New trends in ultrasound of hepatosplenic sarcoidosis

Sarcoidosis is a chronic inflammatory disease, with several issues unexplained and others not completely understood. It can involve ubiquitously any organ or tissue, leading often to a significant morbidity and mortality [1] [2]. The main histopathological finding is represented by non-caseating granulomas, an incomplete degradation of antigenic stimuli, associated with an exuberant macrophage, T- and B-cell activity due to prolonged antigenaemia [3]. By definition, the diagnosis of sarcoidosis is achieved with the presence of appropriate clinical and radiologic thoracic findings, the demonstration of non-caseating granulomas and exclusion of alternative causes [4].

However, symptoms are often nonspecific and radiologic features can be misleading if not included in an appropriate context [5]. Sarcoidosis can present with extrapulmonary disease that manifests with nonspecific findings on imaging. The problem becomes even more complex because extrathoracic involvement, in particular in the liver and spleen, can be isolated without constitutional symptoms or systemic disease. It is not so rare, in fact, to find isolated manifestations that can be misdiagnosed with other diseases [6] [7]. For these reasons, the role of imaging in hepatosplenic sarcoidosis is often reserved for staging and not for diagnostic purposes, by revealing diffuse or focal organ involvement and lymphadenopathy [8]. However, even though the role of conventional imaging such as computed tomography (CT) and magnetic resonance imaging (MRI) has been described widely in the literature [9], there is a lack of information regarding the use of contrast-enhanced ultrasound (CEUS) [6]. No studies have been designed in patients with sarcoidosis and current data is limited on the description of small cases series; however, we have found recently that CEUS has a great potential in the assessment of focal lesions in sarcoidosis, in particular those affecting liver and spleen [10]. Hypo and hyperechoic lesions but also isoechoic masses can be clearly highlighted after injecting contrast agent.

Hypoechoic nodules of the liver appear as variably arterial enhancing and progressively hypoenhancing masses in the portal-venous and late phases; also hypoechoic splenic lesions manifest as progressive hypoenhancing nodules in both arterial and parenchymal phases.

Hyperecoic nodules, both in liver and spleen, are even rarer and no CEUS pattern has been reported so far in the literature; however, we expect similar features between hypo and hyperechoic nodules in view of their similar hypodense pattern on CECT. Isoechoic lesions, that are not evident on conventional B-mode US, can be easily revealed after injecting contrast agent [10]. The different aspect on imaging has already been attributed to a different degree of fibrous tissue in the lesions [11] [12].

Also enlarged lymph nodes can be well assessed. In particular, perihepatic lymphadenopathy shows homogenous enhancement during the arterial phase, suggesting a benign inflammatory pattern [10] [13] [14].

CEUS can overcome several limits of conventional imaging such as CT and MRI in assessing hepatosplenic sarcoidosis. Ultrasound contrast agents (UCAs) are not nephrotoxic and can be used safely in patients at risk (e. g., those with chronic renal disease); additionally, there is no risk of radiation exposure after UCAs administration. This can be particularly helpful in the follow-up of patients with sarcoidosis under corticosteroid therapy, because examinations can be easily repeated to reveal any change in contrast enhancement without any biological risk [10]. As already highlighted, however, current evidence derives from case reports or small descriptions of cases; we hope that future studies will assess reliability of CEUS in patients with sarcoidosis, by comparing CEUS with other techniques such as CT and MRI, and also with histopathological examinations of affected tissues.

The diagnosis of hepatosplenic sarcoidosis represents a challenge for gastroenterologists [15]; an adequate clinical and laboratory evaluation, followed by a correct imaging approach can provide a successful solution for the diagnosis of this disease. CEUS may be a promising imaging technique in this situation, and we anticipate that CEUS will be considered in future trials aimed at assessing hepatic and splenic localization of sarcoidosis. These studies may radically change the approach to this complex disease.

• References

• 1 Valeyre D, Prasse A, Nunes H et al. Sarcoidosis. Lancet 2014; 383 (9923) 1155-67
• 2 Tana C, Giamberardino MA, Di Gioacchino M et al. Immunopathogenesis of sarcoidosis and risk of malignancy: a lost truth?. Int J Immunopathol Pharmacol 2013; 26 (02) 305-313
• 3 James DG. A clinicopathological classification of granulomatous disorders. Postgrad Med J 2000; 76 (898) 457-465
• 4 Statement on sarcoidosis. Joint Statement of the American Thoracic Society (ATS), the European Respiratory Society (ERS) and the World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) adopted by the ATS Board of Directors and by the ERS Executive Committee, February 1999. Am J Respir Crit Care Med 1999; 160 (02) 736-755
• 5 Criado E, Sánchez M, Ramírez J et al. Pulmonary sarcoidosis: typical and atypical manifestations at high-resolution CT with pathologic correlation. Radiographics 2010; 30 (06) 1567-1586
• 6 Tana C, Iannetti G, D’Alessandro P et al. Pitfalls of contrast-enhanced ultrasound (CEUS) in the diagnosis of splenic sarcoidosis. J Ultrasound 2013; 16 (02) 75-80
• 7 Tana C, Iannetti G, Mezzetti A et al. Splenic sarcoidosis remains a diagnostic challenge. J Clin Ultrasound 2014; 42 (03) 156
• 8 Iannuzzi MC, Rybicki BA, Teirstein AS. Sarcoidosis. N Engl J Med 2007; 357 (21) 2153-2165
• 9 Warshauer DM, Lee JKT. Imaging manifestations of abdominal sarcoidosis. Am J Roentgenol 2004; 182 (01) 15-28
• 10 Tana C, Dietrich CF, Schiavone C. Hepatosplenic sarcoidosis: contrast-enhanced ultrasound findings and implications for clinical practice. Biomed Res Int 2014; 926203
• 11 Warshauer DM, Molina PL, Hamman SM et al. Nodular sarcoidosis of the liver and spleen: analysis of 32 cases. Radiology 1995; 195 (03) 757-762
• 12 Hoeffel C, Bokemeyer C, Hoeffel JC et al. CT hepatic and splenic appearances with sarcoidosis. Eur J Radiol 1996; 23 (02) 94-96
• 13 Hirche TO, Hirche H, Cui XW et al. Ultrasound evaluation of mediastinal lymphadenopathy in patients with sarcoidosis. Med Ultrason 2014; 16 (03) 194-200
• 14 Cui XW, Jenssen C, Saftoiu A et al. New ultrasound techniques for lymph node evaluation. World J Gastroenterol 2013; 19 (30) 4850-4860
• 15 Chokoeva AA, Tchernev G, Tana M et al. Exclusion criteria for Sarcoidosis: A novel Approach for An Ancient Disease ?. Eur J Int Med 2014; 25 (10) 120 DOI: 10.1016/j.ejim.2014.10.009.